One of the goals of Gerontological research is to distinguish between human dysfunction caused by disease and dysfunction caused by aging alone. Drugs are commonly used to treat diseases in elderly people and the incidence of adverse drug reactions increases dramatically with advancing age. Iatrogenic disease thus plays a major role in the dysfunction of elderly patients. This study is structured to explore in-depth one form of iatrogenic disease in the elderly: drug induced autoimmunity. The goal of this program is to prospectively define the pharmacokinetics and metabolism of three drugs commonly implicated in autoimmune reactions in elderly patients and to relate such data to potential molecular mechanisms of drug-induced autoimmune reactions and subsequent activation of inflammatory mediators. The specific objectives of this research program are three-fold: 1) to prospectively define the pharmacodynamics in aging patients of phenytoin, hydralazine and procainamide in order to establish age related alterations in drug disposition, efficacy and toxicity of the three agents and to establish a rigorously defined patient population in which to explore molecular mechanisms of subsequent drug induced autoimmune reactions: 2) to relate age associated changes in drug disposition/metabolism to the increased incidence of drug induced autoimmune reactions in the elderly; 3) to isolate drug induced autoantigens and immune complexes in study patients who develop autoimmune reactions and explore the molecular differences between those autoantigens and immune complexes that activate lymphokine production and those that do not.